Studies suggest potent therapeutic effects of rufinamide in bipolar disorder, depressive and anxiety disorders

This study formulates the hypothesis that rufinamide, a drug so far used against epilepsy, may also be effective in bipolar disorder, depressive and anxiety disorders, panic disorder and obsessive-compulsive disorder, eating disorders, and substance use disorders. It is just an hypothesis based on two cases that needs to be confirmed by specific studies.

Rufinamide is a triazole derivative indicated in the USA for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years and older and adults. Rufinamide has activity in the maximal electroshock model and the pentylenetetrazol test, although the ED 50 (median effective dose) is an order of magnitude higher in the pentylenetetrazol test, and in a wide range of other animal models, including seizures induced by GABA-A receptor antagonists, and models of neocortical epilepsy. Based on in vitro studies, the principal mechanism of action of rufinamide is considered to be the modulation of the activity of sodium channels and, in particular, prolongation of the inactive state of the sodium channel. Rufinamide has a low degree of protein binding (34%), and its half-life is approximately 6-10 h, which has led to its recommended twice-daily administration. The most commonly observed adverse experiences seen in association with rufinamide and at a higher frequency than in placebo-treated patients are headache, dizziness, fatigue, somnolence and nausea. This study reports on 2 cases where the off-label use of rufinamide led to marked clinical improvements in patients with complicated psychiatric histories.

The first patient was a woman with bipolar disorder and multiple psychiatric comorbidities (panic disorder, obsessive-compulsive disorder, eating disorder), who had been extraordinarily refractory to treatment and had failed countless pharmacological and nonpharmacological treatment attempts, including ECT. In the context of progressive worsening of her condition, rufinamide 400 mg 1 tablet twice daily was added to her complicated pharmacological regimen, leading to a marked clinical improvement. The patient reported a marked improvement in depressive and obsessive symptoms, a reduction in anxiety and panic attacks, and a significant mood stabilization and reduction in mood swings. The dose was subsequently adjusted to 800 mg twice daily and the patient's improvement persisted over the following 2 months.

The second patient was another woman with bipolar disorder and multiple psychiatric and medical comorbidities (panic disorder, alcohol abuse, chronic pain) who also had been extraordinarily refractory to treatment and had failed countless pharmacological and nonpharmacological treatment attempts. In the context of an acute worsening of her condition, rufinamide 400 mg 1 tablet twice daily was added to her pharmacological regimen, leading to a very rapid (within days) clinical improvement. The patient reported a marked improvement in depressive and anxiety symptoms, significant mood stabilization and reduction in mood swings, and a reduction in craving for alcohol and binge eating.

These 2 cases are highly suggestive of potent therapeutic effects of rufinamide and its metabolites with respect to bipolar disorder, depressive and anxiety disorders, panic disorder and obsessive-compulsive disorder, eating disorders, and substance use disorders. Since these are just anecdotal reports of off-label uses of rufinamide in highly refractory cases, the Authors cannot rule out the possibility that these marked clinical changes were due to nonspecific effects or to the concomitant treatments, which seemed ineffective prior to rufinamide treatment initiation. On the other hand, these observations may merit further investigation of the potential therapeutic benefits of this antiepileptic drug.